Analysis of ultrasonic scans and karyotype of fetuses with holoprosencephaly diagnosed in The Department of Obstetrics & Gynecology of the Postgraduate Center of Medical Education between 1997 & 2005

Objectives: The aim of our study was to determine the risk of aneuploidy and associated malformations in fetuses with holoprosencephaly. We have also analyzed the gestational age during the first examination. Design: We have studied ultrasound reports of fetuses with holoprosencephaly. Materials and Methods: We analyzed 33 cases, diagnosed in the course of the last eight years in our center. All fetuses underwent a detailed ultrasound survey and, in most cases, antenatal karyotyping. In all cases the type of holoprosencephaly was assessed Results: In analyzed fetuses alobar holoprosencephaly was diagnosed in 24, semilobar in 7 and lobar holoprosencephaly in 2 cases. Associated anomalies were detected in 28 (mostly face defects) and chromosomal abnormalities in 12 cases. The median gestational age at the first examination was 25 weeks. No more than 14 examinations had been performed before 24 week. Conclusions: Our findings suggest that in case of fetuses with holoprosencephaly, a detailed ultrasound survey and karyotyping are essential to be performed in all cases. For that reason, patients with fetuses with holoprosencephaly should be diagnosed as early as possible in the referral center

Prenatal diagnosis of craniosynostosis (compound Saethre-Chotzen syndrome phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3–7p15.3, including TWIST1 gene – a case report

Craniosynostosis (a premature fusion of the cranial sutures) occurs with a frequency of 1 in 2100–2500 births and in over 40% cases is caused by known genetic factors – either single gene mutations or chromosomal rearrangements. Cases caused by complex chromosomal abnormalities are uncommon and likely associated with compound phenotype. Saethre–Chotzen syndrome (SCS) [#101400] is caused by TWIST1 gene haploinsufficiency. Its phenotype includes uni– or bicoronal synostosis, short stature, facial dysmorphism and variable anomalies of the hands and feet. Due to its poor sonographic manifestation a prenatal diagnosis of SCS is challenging. We report a case of a prenatally detected craniosynostosis (compound Saethre–Chotzen syndrome phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3–7p15.3, including TWIST1 gene

Wykorzystanie krwi matczynej do transfuzji dopłodowych w terapii konfliktu serologicznego na przykładzie trzech trudnych przypadków

Maternal alloimmunization can lead to hemolytic anemia, hydrops fetalis and even fetal or neonatal death. Intrauterine treatment is possible and effective even though it is associated with some risk. We present a rare method of maternal blood intrauterine transfusions in the therapy of three difficult cases of erythroblastosis fetalis. The aim of this report was to present an alternative to volunteer donors. In severe cases, i.e. in the absence of matching blood types from the donor, in the presence of multiple alloantibodies in the pregnant woman or if multiple transfusions are required, this can be the only therapeutic option. To the best of our knowledge, this has been the first publication on maternal blood donation for intrauterine transfusion in the Polish literature.Konflikt serologiczny może prowadzić do niedokrwistości hemolitycznej, obrzęku, a nawet śmierci płodu lub noworodka. Skuteczne leczenie wewnątrzmaciczne jest możliwe, choć obarczone ryzykiem powikłań. W pracy zaprezentowano rzadko stosowaną metodę wykorzystania krwi matczynej do transfuzji dopłodowych w terapii trzech trudnych przypadków konfliktu serologicznego, pragnąc zwrócić uwagę na alternatywny sposób pozyskania krwi do przetoczeń dopłodowych. W szczególnie ciężkich przypadkach (brak dostępności zgodnej antygenowo krwi od dawcy, obecność kilku rodzajów przeciwciał przeciw krwinkom czerwonym u matki, konieczność wykonania licznych przetoczeń) może być to jedyna opcja terapeutyczna. Według wiedzy autorów jest to pierwsza publikacja dotycząca tej metody leczenia prezentowana w polskim piśmiennictwie

Nieinwazyjna diagnostyka prenatalna najczęstszych aneuploidii na podstawie płodowego DNA we krwi matki – doniesienie wstępne

Objectives: The aim of the study was to present initial results of non-invasive prenatal diagnosis of common aneuploidies of chromosomes 21, 18 and 13 based on cell-free fetal DNA in maternal serum in high-risk patients, and to compare the results with routine karyotyping. Material and methods: Before the invasive procedure, 10 ml of peripheral blood from 10 patients was collected to isolate cell-free fetal DNA and to perform a non-invasive fetal trisomy test (NIFTY provided by Beijing Genomics Institute, BGI, Shenzen, China). Results: Three out of 10 samples showed an abnormal karyotype in traditional karyotyping. There were 9 conclusive NIFTY results. NIFTY detected 1 out of 2 trisomies 18. The quantity of cell-free fetal DNA in maternal plasma in the second probe with trisomy 18 was unsatisfactory for a conclusive NIFTY result. In 1 case traditional karyotyping revealed mosaicism impossible to detect with NIFTY.Cel pracy: Wstępne przedstawienie wyników wykorzystania płodowego DNA z krwi matki w nieinwazyjnej diagnostyce prenatalnej aneuploidii chromosomów 21, 18 i 13 u pacjentek wysokiego ryzyka aberracji chromosomowych u płodu oraz ich porównanie z wynikami klasycznego badania cytogenetycznego. Materiał i metoda: Od dziesięciu ciężarnych pacjentek przed wykonaniem badania inwazyjnego pobrano 10 ml krwi obwodowej celem izolacji pozakomórkowego DNA płodu (cffDNA – cell free fetal DNA) i przeprowadzenia testu NIFTY (Non-Invasive Fetal Trisomy Test; Beijing Genomics Institute, BGI, Shenzen, China). Wyniki: W trzech z dziesięciu próbek w badaniu cytogenetycznym stwierdzono nieprawidłowy kariotyp płodu. Na podstawie płodowego DNA z dziewięciu próbek osocza za pomocą testu NIFTY udało się określić ryzyko aneuploidii u płodu. Wysokie ryzyko aneuploidii prawidłowo oceniono w jednym z dwóch przypadków trisomii chromosomu 18. W drugiej probce podejrzewano wysokie ryzyko trisomii chromosomu 18, ale ilość cffDNA była zbyt mała, aby wynik spełniał standardy producenta. Wykryty w badaniu cytogenetycznym kariotyp mozaikowy z założenia nie mógł zostać wykryty metodą nieinwazyjną. Wnioski: Płodowe DNA z krwi matki może służyć do wykrywania najczęstszych aneuploidii u płodu. Test mógłby posłużyć jako badanie przesiewowe II rzutu, prowadząc do zmniejszenia liczby pacjentek poddawanych badaniu inwazyjnemu

Implementation of Exome Sequencing in Prenatal Diagnosis and Impact on Genetic Counseling: The Polish Experience

This article belongs to the Special Issue Novel Insights into Prenatal Genetic Testing.Background: Despite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling. Methods: In this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021. Results: During the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members. Conclusions: Exome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives.This research was funded by the Ministry of Health, granted to the Center of Postgradu- ate Medical Education, Poland, grant number Minigrant-501-1-106-44-20/MG4 to J.B., and by the National Science Centre, Poland, grant number Miniatura 2—Dec2018/02/X/NZ2/00709 to D.M.info:eu-repo/semantics/publishedVersio

Prenatal diagnosis of Emanuel syndrome – case series and review of the literature

We present three new cases and review of the literature on the prenatal diagnosis of Emanuel syndrome (ES). Twenty-one foetuses have been analysed. In all three cases diagnosed in our department, posterior fossa abnormalities were seen and in one hypoplastic right ventricle was diagnosed at the first trimester scan. Defects of the posterior fossa (62% of foetuses; 13/21) and left diaphragmatic hernia (29% of foetuses; 6/21) are the most frequently reported prenatal findings in ES syndrome. No pattern of specific prenatal ultrasound markers of ES exists. Abnormalities of the posterior fossa are frequent and may be diagnosed as early as in the first trimester of pregnancy. Specific diagnosis can be made only after invasive genetic testing.IMPACT STATEMENT What is already known on this subject? Emanuel syndrome (ES) is a rare genetic disorder. No pattern of specific prenatal ultrasound markers exists. The great majority of cases is diagnosed postnatally and only a few cases of prenatal diagnosis have been published to date. What do the results of this study add? The most frequent structural abnormalities in prenatally detected ES involved central nervous system (80.9%), namely posterior fossa defects (57.1%) and mild ventriculomegaly (23.8%). Other frequent abnormalities include left diaphragmatic hernia (28.6%), renal defects (23.8%) and foetal growth restriction (FGR) (23.8%). What are the implications of these findings for clinical practice and/or further research? Abnormalities of the posterior fossa are the most frequent defects in ES and may be diagnosed as early as in the first trimester of pregnancy. Specific diagnosis can be made only after invasive genetic testing

Prenatal Diagnosis by Array Comparative Genomic Hybridization in Fetuses with Cardiac Abnormalities

Congenital heart defects (CHDs) appear in 8–10 out of 1000 live born newborns and are one of the most common causes of deaths. In fetuses, the congenital heart defects are found even 3–5 times more often. Currently, microarray comparative genomic hybridization (array CGH) is recommended by worldwide scientific organizations as a first-line test in the prenatal diagnosis of fetuses with sonographic abnormalities, especially cardiac defects. We present the results of the application of array CGH in 484 cases with prenatally diagnosed congenital heart diseases by fetal ultrasound scanning (256 isolated CHD and 228 CHD coexisting with other malformations). We identified pathogenic aberrations and likely pathogenic genetic loci for CHD in 165 fetuses and 9 copy number variants (CNVs) of unknown clinical significance. Prenatal array-CGH is a useful method allowing the identification of all unbalanced aberrations (number and structure) with a much higher resolution than the currently applied traditional assessment techniques karyotype. Due to this ability, we identified the etiology of heart defects in 37% of cases

Comparative Genomic Hybridization to Microarrays in Fetuses with High-Risk Prenatal Indications: Polish Experience with 7400 Pregnancies

The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test